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From the Cognitive Neuropharmacology Unit (Dr. Litvan, M. Phipps, and V.L. Pharr) and the Defense and Veteran Head Injury Program (Dr. Salazar), Henry M. Jackson Foundation; and the Medical Neurology Branch (Dr. Hallett) and the Cognitive Neuroscience Section (Dr. Grafman), National Institute of Neurological Disorders and Stroke, National Institutes of Health.
Address correspondence and reprint requests to Dr. I. Litvan, Cognitive Neuropharmacology Unit, The Champlain Building, 6410 Rockledge Drive, Suite 600, Bethesda, MD 20817-1844; e-mail: ilitvan{at}dvhip.org
Objective:— There is no effective treatment for progressive supranuclear palsy (PSP). Because results of immunochemical and pharmacologic studies suggest that the cholinergic system may play a role in the cognitive and motor features of PSP, the authors investigated the effects of donepezil (10 mg/day), an acetylcholinesterase inhibitor, in 21 patients with PSP (mean age ± SD; 65.7 ± 4.7 years) by a randomized, double-blind, placebo-controlled crossover trial.
Methods:— Donepezil and placebo were administered for 6 weeks each with a 1-month washout period. Patients were evaluated before and at the end of each treatment phase. Outcome measures evaluated neuropsychiatric, global cognitive, frontal, memory, motor, and activities of daily living (ADL) status.
Results:— Two patients withdrew during the washout phase because of unrelated medical problems. Donepezil-induced systemic side effects were transient and generally mild. Because of worsening of motor function, three patients received 5 mg/day of donepezil. All patients achieved blood and CSF therapeutic levels of donepezil. While the patients were taking donepezil, their Double Memory Test scores improved, whereas their ADL/mobility scores significantly worsened.
Conclusion:— The findings suggest that acetylcholinesterase inhibitors such as donepezil have at best selective, modest effects on cognition in patients with PSP. In light of its deleterious effects on ADL/mobility, donepezil is not recommended for this patient population.
This article has been cited by other articles:
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  N M Warren, M A Piggott, A J Lees, and D J Burn The basal ganglia cholinergic neurochemistry of progressive supranuclear palsy and other neurodegenerative diseases J. Neurol. Neurosurg. Psychiatry, June 1, 2007; 78(6): 571 - 575. [Abstract] [Full Text] [PDF]
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 L. I. Golbe, B. F. Boeve, B. M. Keegan, and J. E. Parisi An 81-year-old man with imbalance and memory impairment Neurology, April 3, 2007; 68(14): 1147 - 1152. [Full Text] [PDF]
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 N. M. Warren, M. A. Piggott, E. K. Perry, and D. J. Burn Cholinergic systems in progressive supranuclear palsy Brain, February 1, 2005; 128(2): 239 - 249. [Abstract] [Full Text] [PDF]
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 J. L. Cummings Use of Cholinesterase Inhibitors in Clinical Practice: Evidence-Based Recommendations Focus, April 1, 2004; 2(2): 239 - 252. [Abstract] [Full Text] [PDF]
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M. Onofrj and A. Thomas Severe worsening of parkinsonism in Lewy body dementia due to donepezil Neurology, November 25, 2003; 61(10): 1452 - 1452. [Full Text] [PDF]
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C. G. Goetz, S. Leurgans, A. E. Lang, and I. Litvan Progression of gait, speech and swallowing deficits in progressive supranuclear palsy Neurology, March 25, 2003; 60(6): 917 - 922. [Abstract] [Full Text] [PDF]
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